The regulation of adenylate cyclase and phosphodiesterase activity by norepinephrine, histamine, serotonin, dopamine, peptides, prostaglandins, adenosine, calmodulin, guanyl nucleotides, receptors, P-sites, and other factors has been investigated. Such data are fundamental to an understanding of the role of cyclic nucleotides in the central nervous system. High affinity adenosine receptors in brain membranes selectively bind radioactive N6-cyclohexyladenosine. Antagonism of binding of the cyclohexyladenosine by caffeine and other xanthines correlates with the central stimulant properties of these agents. Radioactive 8-phenyl-1, 3-diethylxanthine appears to be a prototype of a ligand for the low affinity adenosine receptor in brain membranes. Forskolin, a diterpene, rapidly and reversibly activates adenylate cyclase in membranes and in intact cells. The activation involves both direct activation of adenylate cyclase and facilitation of receptor-mediated activation of enyzme. The degree of facilitation varies markedly with the nature of the receptor and tissue. Responses to biogenic amines are markedly potentiated by forskolin. Forskolin appears to represent a general tool for the investigation of the physiological role of elevated levels of cyclic AMP in brain and other tissues.